Iron and CF‐related anemia: Expanding clinical and biochemical relationships

Gifford, Alex H.; Miller, S. D.; Jackson, Brian P.; Hampton, Thomas H.; O’Toole, George A.; Stanton, Bruce A.; Parker, H. Worth

doi:10.1002/ppul.21335

Cited by 36 publications

(52 citation statements)

References 22 publications

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“…Inpatient status for this cohort was previously shown to correlate with increased prevalence of cystic fibrosis-related diabetes and low FEV 1 , low serum iron, and high sputum iron levels, a phenotype of more severe disease (8). However, the impact of individual species or interspecies interactions for each of these phenotypes remained unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, both the inpatient and outpatient groups included participants who were either on or off maintenance tobramycin treatment at the time of sample collection. Further clinical description and analysis of this patient cohort was previously reported (8).…”

Section: Resultsmentioning

confidence: 99%

“…The patient cohort studied here includes 39 CF patients recruited as part of a previously reported cross-sectional study (8). At the time of sputum collection, 25 participants were clinically stable (outpatient status) and 14 participants were in a state of clinical worsening (inpatient status).…”

Section: Resultsmentioning

confidence: 99%

“…The study enrollment, assessment of inpatients versus outpatients, and a description of the clinical characteristics of this patient cohort were detailed by Gifford et al (8). Spontaneously expectorated sputum samples were collected during routine visits for outpatient samples.…”

Section: Methodsmentioning

confidence: 99%

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Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability

Filkins

Hampton

Gifford

et al. 2012

Journal of Bacteriology

172

200

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e Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but maintenance treatment with tobramycin did not impact overall diversity. Contrary to the current dogma in the field that Pseudomonas aeruginosa is the dominant organism in the majority of cystic fibrosis patients, Pseudomonas constituted the predominant genera in only half the patient samples analyzed and reported here. The increased fractional representation of Streptococcus in the outpatient cohort relative to the inpatient cohort was the strongest predictor of clinically stable lung disease. The most prevalent streptococci included species typically associated with the oral cavity (Streptococcus salivarius and Streptococcus parasanguis) and the Streptococcus milleri group species. These species of Streptococcus may play an important role in increasing the diversity of the cystic fibrosis lung environment and promoting patient stability.

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability

Filkins

Hampton

Gifford

et al. 2012

Journal of Bacteriology

172

200

View full text Add to dashboard Cite

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“…Iron is a micronutrient vital for bacterial growth but relatively scarce in most infection sites, acting as a limiting factor (5). In contrast, iron levels have been found to be high in CF sputum and correlate negatively with patient outcomes (6). Additionally, pathogen lung colonization in CF patients displays a conserved pattern of succession, with S. aureus predominating early on before being displaced by P. aeruginosa (7).…”

Section: Micronutrients/microorganismsmentioning

confidence: 94%

Iron-Mediated Control of Pseudomonas aeruginosa-Staphylococcus aureus Interactions in the Cystic Fibrosis Lung

Barnabie

Whiteley

2015

J Bacteriol

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Communication is an important factor for bacterial survival, growth, and persistence. Much work has examined both inter-and intraspecies interactions and their effects on virulence. Now, researchers have begun to explore the ways in which host-modulated factors can impact bacterial interactions and subsequently affect patient outcomes. In this issue, two papers discuss how the host environment alters interactions between the pathogens Pseudomonas aeruginosa and Staphylococcus aureus, largely in the context of cystic fibrosis. MICROSCOPIC SOCIETY Just as macroscopic creatures must communicate in order to survive and thrive in the macroscopic world, so too do microorganisms "talk" with each other at the microscopic level. Instead of audio calls and visual cues, bacteria instead rely on the language of signaling molecules. As this method of cellular communication involves large numbers of cells coming to a "consensus" on subsequent group actions, researchers dubbed this behavior "quorum sensing." Classical quorum sensing has been largely focused on autoinduction, wherein a single species produces a signaling molecule unable to induce gene expression until the population grows to a threshold concentration. This phenomenon was first characterized in bioluminescence produced by Aliivibrio (formerly Vibrio) fischeri and has since been identified in a variety of clinically relevant human pathogens. More recent cell-cell communication research has revealed that other kinds of molecules, including metabolites and nutrients present in the growth environment, serve as cues that impact bacterial interactions (1-3). Additionally, interactions between different species have been found to occur in polymicrobial infections where they often form synergistic, virulence-enhancing relationships (4). MICRONUTRIENTS/MICROORGANISMSAs pathogenic bacteria prey upon their host as a living source of nourishment, it is not surprising that available nutrients in the host environment can have a major impact on microbial gene expression. It also follows, then, that such an important regulatory factor might also affect the ways in which bacteria interact within the host. Therefore, a key question is whether the in vitro systems primarily used to study microbial interactions provide relevant insights into the ways in which microbes interact in the host.This issue of the Journal of Bacteriology features two papers that explore the impact of host-provided nutrients further in the context of iron's ability to modulate Pseudomonas aeruginosa/Staphylococcus aureus interactions in the cystic fibrosis (CF) lung. Iron is a micronutrient vital for bacterial growth but relatively scarce in most infection sites, acting as a limiting factor (5). In contrast, iron levels have been found to be high in CF sputum and correlate negatively with patient outcomes (6). Additionally, pathogen lung colonization in CF patients displays a conserved pattern of succession, with S. aureus predominating early on before being displaced by P. aeruginosa (7). Although it has b...

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Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: Trends and biomarker correlations

2013

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Summary Introduction Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Methods Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. Results CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1%). At early and late CFPE, serum IGF-1 was directly correlated with FEV1%, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. Conclusions This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE.

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Iron and CF‐related anemia: Expanding clinical and biochemical relationships

Cited by 36 publications

References 22 publications

Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability

Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability

Iron-Mediated Control of Pseudomonas aeruginosa-Staphylococcus aureus Interactions in the Cystic Fibrosis Lung

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: Trends and biomarker correlations

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